The cellular processes which regulate the uptake, storage, utilization and excretion of copper are to be established. Isolated rat liver parenchymal cells, and the fungal cells by Dactylium dendroides will be used. Kinetics of uptake and factors which influence the kinetics of uptake into liver cells will be carefully evaluated. The time dependence for copper entry into each liver cellular organelle compartment will also be examined. Copper proteins in particulate subcellular fractions will be identified. With the fungal cells, the distribution of limited amounts of copper into galactose oxidase, superoxide dismutase and cytochrome oxidase will be determined. The activity of the manganese superoxide dismutase will be followed as the copper concentration is made limiting. Relationships between normal copper metabolism in liver cells and Wilson's Disease will also be carefully considered. Moreover, the physiological, biochemical and pathological characteristics of a liver disease which is characterized be elevated copper levels in Bedlington Terriers will be carefully evaluated as an animal model for Wilson's Disease.